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BPK 312 Nutrition for Fitness & Sport Lecture 3 Nutrient Roles in Bioenergetics 1. Learning Objectives for Lecture 3 2. Bioenergetics/Conservation of Energy 3. Redox Reactions 4. ATP/Phosphocreatine 5. Cellular Oxidation/Electron Transport/Oxidative Phosphorylation 6. Energy Release from Macronutrients 7. The Metabolic Mill 1 1. Lecture 3 Learning Objectives (LO3) LO3-1: Define bioenergetics and give a description of the nutritionenergy interaction, energy transfer from macronutrients and cellular respiration. LO3-2: Define and explain oxidation-reduction reactions as well as how they are important in energy transfer from macronutrients to ATP. LO3-3: Explain how phosphocreatine and high energy phosphate bonds allow short term, explosive activity. LO3-4: Explain the details of how electron transport in the respiratory chain and oxidative phosphorylation allow the transfer of energy from macronutrients to ATP. LO3-5: Explain and describe the steps of energy transfer from: (i) glycogen and glucose to ATP in glycolysis, (ii) from coenzymes to high energy phosphate bonds in the citric acid cycle and (iii) from lactate in the Cori Cycle. LO3-6: Name the sources of fat for catabolism and describe the steps in transfer of energy from triacylglycerols in beta-oxidation to the electron transport chain for ATP production. LO3-7:Explain deamination, transamination and how the carbon ‘skeletons’ from amino acids are catabolized to give gluconeogenic as 2 well as ketogenic intermediates for energy transfer. 2. Bioenergetics & Conservation of Energy § Bioenergetics refers to flow of energy within a living system. § Aerobic chemical reactions do & anaerobic chemical reactions do not require oxygen. § Energy is transferred from the sun to plants by photosynthesis using chlorophyll, H2O & CO2 to produce carbohydrates (CHO) including glucose. Overall equation for photosynthesis: § Cellular respiration in animals allows recovery of food chemical energy stored in plants § Herbivores, carnivores and omnivores transfer energy transfer from different food sources § Image Source: https://en.wikipedia.org/w/index.php?title=Photosynthesis&oldid=759051544 3 2. Bioenergetics & Conservation of Energy ‘On engraisse pas les cochons à l'eau claire’ Jeanne Beauregard, né Archambault, Calixa-Lavallée, Qc, 1908-1985 Energy and Laws of Thermodynamics § First law – Energy is neither created nor destroyed, but instead, transforms from one state to another without being used up. § There are six forms of interchangeable energy states: • Chemical, Light, Electric, Mechanical, Heat, Nuclear Biologic Work Takes one of three forms: § • Mechanical work of muscle contraction • Chemical work for synthesizing molecules • Transport work that concentrates diverse substances in body fluids 4 2. Bioenergetics & Conservation of Energy Recall Potential Energy and Kinetic Energy § Potential energy (PE) refers to energy associated with a substance’s structure or position. § Kinetic Energy (KE) refers to energy of motion. § PE and KE constitute the total energy of any system. § Releasing PE transforms it into KE of motion. Energy transformation in the human body depend on: • (i) Oxidation-reduction (redox) reactions & (ii) Chemical reactions that conserve & liberate energy in Adenosine Triphosphate (ATP) 5 3. Redox Reactions § Oxidation–reduction reactions couple: • Oxidation = a substance loses H+, electrons or oxygen giving a ↑valence • Reduction = a substance gains electrons giving a ↓valence § Redox reactions power the body’s energy transfer processes. LDH MAXIMAL STRENUOUS MODERATE LIGHT LDH (Lactate Dehydrogenase = LDH) Fig 4-5: Example of a redox reaction during intense exercise - the reduction of pyruvate to give lactate & subsequent oxidation of lactate to give pyruvate during recovery cf slide 22 6 4. Adenosine Triphosphate (ATP) & Phosphocreatine (PCr) • ATP is the body’s primary energy carrier molecule that captures free energy high energy phosphate bonds Examples of work carried out in the body using ATP Digestion Circulation 2 outermost phosphate bonds are ‘high energy’ phosphate bonds. • Splits rapidly without O2 • Only 80-100 g of ATP stored in body ∴ there is a continual resynthesis of ATP Nerve Conduction Glandular Muscle Contraction Tissue Synthesis Fig 4-8: Adenosine Triphosphate (ATP), the body’s energy currency that powers all biological work 7 4. Adenosine Triphosphate (ATP) & Phosphocreatine (PCr) § Adenosine TriPhosphate (ATP) is the energy currency of body cells & it contains high energy phosphate bonds § Potential energy (PE) is extracted from macronutrients in food & conserved within phosphate bonds within ATP. § Chemical PE in ATP powers all biologic work. • Adenosine TriPhosphatase (ATPase) • rapid anaerobic energy supply ATP + H2O ATPase → Fig 4-7: Simplified image of ATP ADP + Pi + 7.3 kcal/mole 8 4. Adenosine Triphosphate (ATP) & Phosphocreatine (PCr) Phosphocreatine (PCr): The Energy Reservoir § In addition to ATP, PCr is another high-energy phosphate compound. § PCr quickly releases large amounts of energy when bonds between creatine & phosphate are broken. § Cells store 4–6 x more PCr than ATP § Is a reservoir of high-energy phosphate bonds, for shortterm 8-10 s explosive, all out muscular exercise ATPase Creatine Phosphokinase Fig 4-9: ATP & PCr sources of anaerobic § Phosphorylation gives energy phosphate bond energy. Energy released transfer in phosphate bonds from splitting PCr helps resynthesize ATP from ADP & Pi; Adenosine triphosphatase 9 (ATPase) 5. Cellular Oxidation, Electron Transport Chain (ETC) & Oxidative Phosphorylation ACTIVATION ENERGY sudden release of all chemical energy BURNING OF GLUCOSE ACTIVATION ENERGY slow step-wise release of chemical energy CELLULAR OXIDATON OF GLUCOSE 10 Fig 4-6: Burning glucose in a fire vs. cellular oxidation of glucose 5. Cellular Oxidation, Electron Transport Chain (ETC) & Oxidative Phosphorylation § Most energy for ATP phosphorylation is from oxidation of hydrogen (H) from macronutrients, CHO, lipids & protein § Constitutes the mechanism for aerobic energy metabolism § Involves the transfer of hydrogen atoms & electrons • Loss of hydrogen= oxidation & gain of hydrogen=reduction • Highly specific dehydrogenase co-enzymes are reduced with H from macronutrients • Nicotinamide Adenine Dinucleotide (NAD+) from niacin (Vit B3) • Flavin Adenine Dinucleotide (FAD) from riboflavin (Vit B2) • NADH & FADH2 are 2 high energy molecules carrying H & their electrons § Mitochondria contain cytochrome carrier molecules on their inner membrane that remove electrons from H & pass them to O2 § Electron transport by cytochromes is the ‘respiratory chain’ Chemical Reactions in Mitochondria Animation Button nb change ‘create to ‘transfer’ of energy in this animation http://download.lww.com/wolterskluwer_vitalstream_com/animation_library/HP-03-mitochondria/mitochondria.html 11 5. Cellular Oxidation, Electron Transport Chain (ETC) & Oxidative Phosphorylation Oxidative Phosphorylation § Refers to energy transfer through phosphate bonds § Most of the energy for ATP phosphorylation comes from oxidation of carbohydrates, lipids, and proteins. § Oxidative phosphorylation synthesizes ATP by transferring H & electrons from NADH and FADH2 to oxygen. § >90% of body’s ATP synthesis Fig 4-10: Schematic diagram for oxidation of hydrogen from NADH & FADH2 for subsequent electron transport for the reduction of O2. 12 5. Cellular Oxidation, Electron Transport Chain (ETC) & Oxidative Phosphorylation Electron Transport & Oxidative Phosphorylation 1 Cytochrome 2 e- 2 Cytochrome 2eCytochrome 2e- 3 Cytochrome 2eCytochrome 2e- Electron Transport Animation Button http://download.lww.com/wolterskluwer_vitalstream_com/animation_library/HP-15-electron_transport/electron_transport.html Fig 4-11: In the body chemical energy is liberated with each of 3 hydrogen/electron pairs from NADH & FADH2 are shuttled by 5 mitochondrial cytochromes; cytochromes are Fe 13 containing proteins. This energy is conserved in ATP in high energy phosphate bonds. 5. Cellular Oxidation, Electron Transport & Oxidative Phosphorylation Electron Transport Chain (ETC) & Oxidative Phosphorylation • Theoretical value for aerobic ATP production from oxidation of H & subsequent phosphorylation is: NADH + H+ + 3 ADP + 3 Pi + ½ O2 → NAD+ + H2O + 3 ATP • ATP needs to be transported out of the mitochondria at the cost of some ATP • On average the net yield is 2.5 ATP synthesized per NADH, when FADH2 donates H this gives on average a net yield of 1.5 ATP synthesized from each hydrogen pair 14 5. Cellular Oxidation, Electron Transport Chain (ETC) & Oxidative Phosphorylation Efficiency of Electron Transport Chain (ETC) & Oxidative Phosphorylation • Formation of each mole of ATP conserves ~ 7 kcal of energy • Since 2.5 moles ATP is produced per mole of NADH then 2.5 x 7 kcal = ~18 kcal is conserved as chemical energy • The relative efficiency is ~34% for transferring chemical energy by ETC-oxidative phosphorylation since 1 mole of NADH liberates 52 kcal, i.e. ~18 kcal/52 kcal x 100 = ~34%. • Remaining 66% of this energy is dissipated as heat 15 5. Cellular Oxidation, Electron Transport Chain (ETC) & Oxidative Phosphorylation Role of Oxygen in Energy Metabolism • 3 conditions for ATP re-synthesis using energy from macronutrients – Cond. 1: Availability of reduced NADH & FADH2 in tissues – Cond. 2: Presence of oxidizing agent O2 in the tissues – Cond. 3: Sufficient concentration of the enzymes & mitochondria in the tissues to ensure energy transfer reactions proceed at their appropriate rate • Oxygen is the final electron acceptor in the respiratory chain & combines with hydrogen to form water. • Strenuous Exercise – In Cond. 2 if there is inadequate O2 in the tissues or in Cond 3 if the rate of delivery of O2 is inadequate these give an imbalance between H release & acceptance by O2, i.e. its reduction. – Electron flow down ETC backs up, H accumulates & lactate forms as give in Fig 4-15 on a following slide in this lecture. 16 6. Energy Release from Macronutrients Sources for ATP formation include: i. Glucose derived from liver glycogen ii. Triacylglycerol & glycogen molecules stored within skeletal muscle cells/fibers iii. Free fatty acids (FFA) derived from triacylglycerol in liver and adipocytes that enter the bloodstream for delivery to active muscle iv. Intramuscular & liverderived carbon skeletons of amino acids Fig 4-12 17 6. Energy Release from Macronutrients Intramuscular Energy Stores Fig 4-13: Macronutrient Fuel Sources Mitochondrion Glycogen Glucose Citric Acid Cycle aa ATP TAG Glucose Deaminated aa FFA • • • • • FFA Liver produces rich sources of amino acids (aa) & glucose (glycogen) Adipocytes give large amounts of free fatty acids (FFA) These compounds are released into blood & are carried to skeletal m. Most energy transfer takes place in mitochondria within skeletal m. Intramuscular energy sources include ATP, PCr, Triacylglycerol (TAG), 18 glycogen & carbon skeletons from aa’s 6. Energy Release from Macronutrients Energy Release from Carbohydrates C6H12O6 + 6 O2 → 6CO2 + 6H2O - 686 kcal/mol § 1° function of CHO is to supply energy for cellular work. § in a bomb calorimeter the complete breakdown of 1 mol of glucose of 180 g liberates 686 kcal of energy • Synthesis of 1 mol ATP needs 7.3 kcal of energy • All energy in glucose oxidation could give 94 mol of ATP • In muscle phosphate bonds conserve only 34%, i.e. 34% of 686 kcal/mol = 233 kcal/mol of energy in ATP bonds with the remainder dissipated as heat. • ∴ 1 mol of glucose breakdown gives 233 kcal/7.3 kcal x mol-1 = 32 mol of ATP 19 6. Energy Release from Macronutrients Glucose Degradation Occurs in two stages: 1. Anaerobic: Glucose breaks down relatively rapidly to 2 molecules of pyruvate in the reactions of glycolysis 2. Aerobic: Pyruvate degrades further to carbon dioxide and water in the reactions of the citric acid cycle 20 6. Energy Release from Macronutrients Glycolysis 1 1 § Substrate-level phosphorylation in glycolysis gives net gain of 2 ATP 2. Glucose 6Phosphate isomerase 3 http://download.lww.com/wolterskluwer_vitalstream_com/animation_library/HP-02-glycolysis/ glycolysis.html § Glycolysis gives 5-10% of total ATP from a glucose molecule 1. Hexokinase 2 Glycogen phosphorylase § In cytosol & anaerobic cond. Fig 4-13 ENZYMES 3. Phosphofructokinase 4 5 4. Aldolase 6 7 § Hydrogen release in glycolysis gives 2 NADH 8 § for max exercise <90 s 9 § Glycogenolysis gives net gain 3 ATP b/c 1st step bypassed § Lactate formation 10 5. Triosephosphate isomerase 6. Glyceraldehyde 3- phosphate dehydrogenase 7. Phosphoglycerate kinase 8.Phosphoglycerom utase 9. Enolase 10. Pyruvate kinase 21 6. Energy Release from Macronutrients Lactate Formation & Use • In heavy exercise when energy demand exceeds O2 supply, ETC can’t process all NADH • Depends on reaction 6 in glycolysis & for NAD+ availability to oxidize ‘3-phosphoglyceraldehyde’ Lactate Dehydrogenase = LDH • dramatically slows glycolytic rate & ↑ lactic acid production results • Lactate is a valuable source of chemical energy in the Cori Cycle • nb at physiological pH lactic acid dissociates to lactate & H+ Fig 4-15: Lactic Acid Formation when excess H+ from NADH temporarily combines with pyruvate. This frees NAD+ to accept more H+ from glycolysis, cf slide 6 22 6. Energy Release from Macronutrients Cori Cycle • Lactate is a valuable source of chemical energy during exercise 1. Lactic acid from skeletal muscle enters venous circulation & dissociates to lactate & H+ 2. Lactate enters liver where it is converted to pyruvate & then via gluconeogenesis, there is a resynthesis of glucose. 3. Blood glucose as well as muscle & liver glycogen can subsequently be maintained. 4. Glucose is released from liver to arterial blood to active skeletal muscle. http://download.lww.com/wolterskluwer_vitalstream_com/ animation_library/HP-25-cori_cycle/cori_cycle.html 3 2 Fig 4-16 Glucose 4 1 Cori Cycle Animation Button 23 6. Energy Release from Macronutrients Citric Acid Cycle (CAC) Fig 4-18 § 2nd stage of CHO breakdown is the CAC. § Irreversible joining of pyruvate with CoA, a Vit. B derivative, from Vit B6 or pantothenic acid, to acetyl-CoA § This releases 2 H atoms to reduce both NAD+ & FAD oxaloacetate malate Citric Acid Cycle Animation citrate Button fumarate isocitrate Succinate e.g. Pyruvate + NAD+ + CoA → acetyl-CoA + CO2 + NADH + H+ § The acetyl portion of acetyl-CoA joins with oxaloacetate to form citrate from citric acid. § Each acetyl-CoA gives 2 CO2 & 4 pairs of hydrogen atoms, plus 1 high energy Guanosine-5'triphosphate (GTP) Succinyl-CoA oxalosuccinate α-ketoglutarate http://download.lww.com/ wolterskluwer_vitalstream_ com/animation_library/ HP-16-citric_acid/ citric_acid_cycle.html 24 6. Energy Release from Macronutrients Fig 4-17- Schematic Diagram of hydrogen formation & subsequent oxidation during aerobic energy metabolism. Phase 1: CAC generates H atoms during breakdown of acetyl CoA Phase 2: ATP is reformed when these H’s are oxidized via aerobic electron transport oxidative phosphorylation 25 6. Energy Release from Macronutrients Fig 4-19: Net Yield of 32 ATP molecules during complete oxidation of 1 glucose molecule through glycolysis, the CAC & electron transport chain 26 6. Energy Release from Macronutrients Energy Release from Fat – Lipolysis Lipolysis Animation § Stored fat represents the body’s biggest source of PE. § Energy sources for fat catabolism include: i. Triacylglycerol stored directly in skeletal m. fiber http:// download.lww.com/ wolterskluwer_vitalstr eam_com/ animation_library/ HP-26-triacylglycerol/ triacylglycerol.html ii. Circulating triacylglycerol (TAG) in lipoprotein complexes iii. Circulating free fatty acids Hormone Sensitive Lipase TAG + 3 H2O → 3,5 cyclic monophosphate (cAMP) glycerol + 3 fatty acids 3 steps in lipoysis, steps 1&2 with HSL, Step 3 with HSL & monoglyceride lipase • cAMP Activation: stimulated by epinephrine, norepinephrine (e.g. exercise), glucagon, growth hormone + inhibited by lactate, insulin & ketones • these circulating factors don’t enter cell but activate cAMP & Hormone Sensitive Lipase 27 6. Energy Release from Macronutrients Adipocytes Fig 4-20: Fat storage & mobilization or lipolysis Fat Mobilzation Animation § TAG fat droplets takeup to 95% of adipocyte volume &is major FFA source § Lipase stimulates glycerol & FFA release from adipocytes Lipase § FFA bind to albumin in the plasma http:// download.lww.com/ wolterskluwer_vitalstre am_com/ animation_library/ HP-17-fat_mobilization/ fat_mobilization.html § Long chain fatty acids enter muscle fibers by diffusion or by protein mediated transport &: (i) form intracellular TAG (ii) bind to CoA & then to carnitine by actions of carnitineacyl-CoA transferase I & II fatty acids enter mitochondria (iii) Carnitine + fatty acyl-CoA à acylcarnitine + CoA (iv) end product is Acetyl-CoA à CAC & ETC to give ATP (iv) ↑[Acetyl-CoA]/[CoA] ratio ↓FA transfer to mitoch. § Short & medium chain FA diffuse freely into the mitochondria 28 6. Energy Release from Macronutrients Breakdown of Glycerol and Fatty Acids § Glycerol • Provides carbon skeletons for glucose synthesis, enters glycolytic pathway as 3-phosphoglyceraldehyde to give ATP by substrate-level phosphorylation § Fatty acids • Beta (ß)-oxidation for fatty acid oxidation converts a free fatty acid to multiple acetyl-CoA molecules. • H+ released during fatty acid catabolism is oxidized through the respiratory chain. • Note CAC rate depends on concentration of its intermediates, including oxaloacetate & malate, that are derived from CHO. • A low CHO diet can limit fatty acid oxidation, due a slow rate of the citric acid cycle. C15H32O2 + 23 O2 → 16CO2 + 16H2O + 2397 kcal 29 6. Energy Release from Macronutrients Breakdown of Glycerol and Fatty Acid Fragments Electron transport chain accepts pairs of hydrogen from glycolysis, citric acid cycle and ß-oxidation Fig 4-21: General scheme of glycerol & fatty acid fragment breakdown 30 6. Energy Release from Macronutrients Energy Release from Protein § Protein plays a role as an energy substrate during endurance activities and heavy trainings. § Deamination: Nitrogen is removed from the amino acid by the liver § Transamination: when an amino acid is passed to another compound § remaining carbon skeletons enter metabolic pathways to produce ATP. § especially evident for the branched chained amino acids leucine, isoleucine, valine, glutamine & aspartate § Excessive intake of protein is converted to body fat. 31 6. Energy Release from Macronutrients A. Alanine Structure B. Transamination • The nitrogen containing amine group is transferred to other compounds • Allows availability of the carbon skeleton to enter into energy metabolism • e.g. the compound enters into the citric acid cycle http://download.lww.com/ wolterskluwer_vitalstream_com/ animation_library/HP-23-transamination/ transamination.html Transamination Animation Glutamate Pyruvate Glutamine transaminase α-ketoglutaric acid Alanine 32 Fig. 1-16 A: Chemical structure of aa alanine B: Transamination 6. Energy Release from Macronutrients Glucogenic & Ketogenic Amino Acids • Carbon skeletons of amino acids that form pyruvate or directly enter the citric acid cycle are glucogenic because they can form glucose • Carbon skeletons of amino acids that form acetyl-CoA are ketogenic because they can’t form glucose molecules but rather synthesize fat Fig 4-21: Glucogenic and ketogenic amino acids. 33 6. Energy Release from Macronutrients Deamination Glucose–Alanine Cycle Animation Button Gluconeogenesis Alanine Transaminase • In prolonged exercise this cycle accounts for 10-15% of total exercise energy requirement • after 4 h of continuous light exercise alaninederived glucose accounts for 45% of the livers total glucose release Fig. 1-20: Glucose-Alanine Cycle http://download.lww.com/wolterskluwer_vitalstream_com/animation_library/ HP-09-alanine_glucose/alanineglucose.html 34 7. The Metabolic Mill § The citric acid cycle is a vital link between food energy and the chemical energy of ATP. § The citric acid cycle also provides intermediates that cross the mitochondrial membrane into the cytosol to synthesize bio-nutrients. 35 BPK 312 Nutrition for Fitness & Sport Lecture 3 Summary Slide Nutrient Roles in Bioenergetics 1. Learning Objectives for Lecture 3 2. Bioenergetics/Conservation of Energy 3. Redox Reactions 4. ATP/Phosphocreatine 5. Cellular Oxidation/Electron Transport/Oxidative Phosphorylation 6. Energy Release from Macronutrients 7. Metabolic Mill 36